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Toxicol Sci

Title:		From the Cover: Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants Decreased p-beta-Cateninser675 Expression and Its Interaction With E-Cadherin in the Mammary Glands of Lactating Rats
Author(s):		Dianati E; Wade MG; Hales BF; Robaire B; Plante I;
Address:		"INRS, Institut Armand-Frappier, Laval, Quebec, Canada. Centre de Recherche Biomed, Universite du Quebec a Montreal, Montreal, Quebec, Canada. Health Canada, Environmental Health Science and Research Bureau, Ottawa, Ontario, Canada. Department of Pharmacology and Therapeutics. Department of Obstetrics and Gynecology, Faculty of Medicine, McGill University, Montreal, Quebec, Canada"
Journal Title:		Toxicol Sci
Year:		2017
Volume:		159
Issue:		1
Page Number:		114 - 123
DOI:		10.1093/toxsci/kfx123
ISSN/ISBN:		1096-0929 (Electronic) 1096-6080 (Print) 1096-0929 (Linking)
Abstract:		"Proper mammary gland development and function require precise hormonal regulation and bidirectional cross talk between cells provided by means of paracrine factors as well as intercellular junctions; exposure to environmental endocrine disruptors can disturb these processes. Exposure to one such family of chemicals, the brominated flame retardants (BFRs), is ubiquitous. Here, we tested the hypothesis that BFR exposures disrupt signaling pathways and intercellular junctions that control mammary gland development. Before mating, during pregnancy and throughout lactation, female Sprague-Dawley rats were fed diets containing that BFR mixture based on house dust, delivering nominal exposures of BFR of 0 (control), 0.06, 20, or 60 mg/kg/d. Dams were euthanized and mammary glands collected on postnatal day 21. BFR exposure had no significant effects on mammary gland/body weight ratios or the levels of proteins involved in milk synthesis, epithelial-mesenchymal transition, cell-cell interactions, or hormone signalling. However, BFR exposure (0.06 mg/kg/d) down-regulated phospho-ser675 beta-catenin (p-beta-catSer675) levels in the absence of any effect on total beta-catenin levels. Levels of p-CREB were also down-regulated, suggesting that PKA inhibition plays a role. p-beta-catSer675 co-localized with beta-catenin at the mammary epithelial cell membrane, and its expression was decreased in animals from the 0.06 and 20 mg/kg/d BFR treatment groups. Although beta-Catenin signaling was not affected by BFR exposure, the interaction between p-beta-catSer675 and E-cadherin was significantly reduced. Together, our results demonstrate that exposure to an environmentally relevant mixture of BFR during pregnancy and lactation decreases p-beta-catser675 at cell adhesion sites, likely in a PKA-dependant manner, altering mammary gland signaling"
Keywords:		"Animals Bromine/*chemistry Cadherins/*metabolism *Environmental Exposure Female Flame Retardants/*toxicity *Lactation Mammary Glands, Animal/metabolism Pregnancy Rats Rats, Sprague-Dawley Signal Transduction beta Catenin/*metabolism brominated flame retar;"
Notes:		"MedlineDianati, Elham Wade, Michael G Hales, Barbara F Robaire, Bernard Plante, Isabelle eng RHF 100625/CIHR/Canada Research Support, Non-U.S. Gov't 2017/09/15 Toxicol Sci. 2017 Sep 1; 159(1):114-123. doi: 10.1093/toxsci/kfx123"